Experimental studies on potential utility of Pimobendan in arsenic induced cardiovascular dysfunction in wistar rats
Prashantkumar Waghe, Dr. Prakash Nadoor, Dr. Vijaykumar M, Dr. Shridhar NB, Dr. Pavithra BH, Dr. Vinay P Tikare and Dr. Rashmi Rajashekaraiah
Today, contamination of drinking water with arsenic is a burning public health issue of global significance. Among the various deleterious effects of arsenic, cardiovascular disorders in the exposed population require urgent therapeutic intervention. The present study was aimed to assess whether pimobendan, a phosphodiesterase (PDE) - III inhibitor can attenuate the arsenic-induced cardiovascular dysfunction and to assess the involvement of mechanistic pathways related to reactive oxygen species (ROS) and nitric oxide (NO) signaling in rats. Wistar rats were exposed to arsenic through drinking water (100 ppm) for 90 days. These rats were treated with pimobendan (1 mg/kg) by oral gavage during the last 30 days of exposure to arsenic. At term, after overnight fasting, the experimental rats were sacrificed (91st day) and the aorta and heart tissues were dissected out to determine various parameters. Arsenic exposure favored the production of ROS such as O2͞● and decreased the activities of SOD, CAT, GPx, GR, and GSH content, thus leading to lipid peroxidation (LPO). Pimobendan administration restored the activities of enzymatic (SOD, CAT, GPx, and GR) and the level of GSH in the aorta and heart of arsenic exposed rats and reduced LPO. Experimental rats exposed to arsenic resulted in increased iNOS-derived nitrite production, while pimobendan significantly decreased its level. Similarly, arsenic-induced increase in IL-1β, IL-6, and TNF-α was significantly (p< 0.05) attenuated by pimobendan in the aorta and heart. In summary, the study revealed that sub-chronic exposure to arsenic can induce oxidative stress in rat aorta and heart leading to cardiovascular dysfunction, and pimobendan has the potential to ameliorate the arsenic-mediated alterations through the restoration of redox homeostasis and NO signaling.
How to cite this article:
Prashantkumar Waghe, Dr. Prakash Nadoor, Dr. Vijaykumar M, Dr. Shridhar NB, Dr. Pavithra BH, Dr. Vinay P Tikare, Dr. Rashmi Rajashekaraiah. Experimental studies on potential utility of Pimobendan in arsenic induced cardiovascular dysfunction in wistar rats. Pharma Innovation 2021;10(9):1382-1392.